Visualization and localization of message, protein, or structural change resulting from gene expression is an essential step in evaluating the efficacy of successful gene transfer into cells and tissues. This process varies from studies of whole tissues, defining structural correction of pathological phenotype, to definition of message or protein within a cell/tissue to high resolution observations of successful subcellular passaging and presentation of protein. The Structural Biology Imaging Center, in which this core service will be performed, is designed with this function in mind. It is equipped to perform a complete spectrum of optical methods including all principal light and electron microscopic methods essential to this program project. At the light microscopic level, these include histological, immuno-histological, and in situ hybridization technologies. At the electron microscopic level, we will provide fine structural and immuno-electron microscopic evaluation of specimens as a natural extension of the light microscopic analyses. Furthermore, our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate earlier, possibly quite subtle qualitative changes. This core will be used extensively by all projects, though the imaging tools used will vary from project to project. Preliminary data have shown the validity of these approaches, and we expect a very significant increase in the use of optical technique by each project within the formal setting of this program.